1. Field of the Invention
The present invention generally relates to antagonism of neuromuscular blockade, and more particularly to antagonism of nondepolarizing blockade with a balanced combination of edrophonium and atropine.
2. Description of the Prior Art
Muscle relaxation agents are usefully administered to patients during a great variety of medical procedures, and may generally be characterized as either depolarizing agents or nondepolarizing agents. Nondepolarizing agents provide muscle relaxation for a longer duration than do depolarizing agents, and are generally curare-like drugs such as pancuronium, d-tubocurarine, metocurine, gallamine, vecuronium and atracurium.
Following a procedure where a nondepolarizing agent has been utilized, it is usually desirable that the neuromuscular blockade be antagonized when muscle relaxation is no longer necessary. Presently used antagonists are, for example, anti-cholinesterase drugs such as neostigmine (in combination with an anticholinergic) or pyridostigmine (in combination with an anticholinergic). These prior art compositions are occasionally associated with tachycardia, bradycardia and other dysrhythmias of atrial, nodal and ventricular origin. However, use of the anticholinesterase drugs as antagonists (without an anticholinergic) invariably leads to muscarinic effects such as bradycardia, or slowing of the heart rate, and hence a tendency for blood pressure to fall.
Edrophonium is a reversal inhibitor of acetylcholinesterase, but had been believed to have a brief duration of antagonism, thus allowing possible recurrence of neuromuscular blockade. It was recently reported that a controlled, two minute infusion of edrophonium (0.5 mg/kg) in combination with atropine (1.0 mg) during operative procedures with six patients appeared to provide adequate antagonism of neuromuscular blockade. However, thirty seconds following the start of the infusion the heart rate was observed to decrease, and thirty seconds later a tachycardia developed. Morris, et al., Anesthesiology, Vol. 54, pp. 399-402 (May, 1981).